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PLK1 (polo-like kinase 1 (Drosophila))

Identity

Other namesPLK
STPK13 (SERINE/THREONINE PROTEIN KINASE 13)
HGNC (Hugo) PLK1
Location 16p12.1
Location_base_pair Starts at 23597702 and ends at 23609189 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order Genes flanking PLK1 in centromere to telomere direction on 16p12 are:
  • UBPH, 16p12, similar to ubiquitin binding protein
  • NDUFAB1, 16p12.1, NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1,8kDa
  • FLJ21816, 16p12.1, hypothetical protein FLJ21816
  • MGC3248, 16p12.1, dynactin 4
  • PLK1, 16p12.1, polo-like kinase 1 (Drosophila)
  • LOC388226, 16p12.1, similar to endoplasmic reticulum (ER) to nucleus signaling 2; inositol-requiring 1 (Yeast homologue)
  • LOC63928, 16p12.1, hepatocellular carcinoma antigen gene 520
  • PRKCB1, 16p11.2, protein kinase C, beta 1
  • CACNG3, 16p12-p13.1, calcium channel, voltage-dependent, gamma subunit 3
    		•
    Note Polo like kinases belong to serine/threonine kinases that are conserved from yeast to human cells. Polo like kinases exhibit important roles in key cellular events regulating cell cycle progression and cell division such as centrosome maturation, cdc2 activation, mitotic spindle formation, regulation of the anaphase promoting complex, chromosome segregation, cytokinesis, DNA damage response pathways and apoptosis.

    DNA/RNA

     
      The alignment of PLK1 mRNA (NM_005030) to its genomic sequence NC_000016).
    Description PLK1 mRNA spans approximately 11.5 kb and has 10 exons. The sizes of the exons 1 to 10 are 461, 169, 145, 94, 220, 156, 78, 155, 183 and 508 bps.
    Transcription PLK1 mRNA (NM_005030) is 2204 bp. PLK1 expression is believed to reach its peak value in mitosis in the cell cycle. It is highly expressed in actively proliferating tissues such as those in the placenta, spleen, ovary, and testis. High expression of PLK1 is also detected in various neoplastic tissues. Northern blot analysis reveals low or undetectable levels of PLK1 transcript in most other adult tissues (e.g.: brain, thymus, liver, lung, pancreas, heart, kidney, stomach, intestine and skin).
    Pseudogene Mouse Plk gene maps to Chromosome 7 and the processed pseudogene to mouse Chromosome 5. No human pseudogene for PLK1 has been reported.

    Protein

    Description Protein consists of 603 amino acids and is 66kDa. In addition to the N-terminus kinase domain, there are two conserved polo-box regions of 30 amino acids at the C-terminus. Kinase activity is regulated at least in part, by the polo-boxes that are functionally important for both auto-inhibition and sub-cellular localization.
    Expression PLK1 protein becomes a target of the anaphase-promoting complex/cyclosome and is degraded by the ubiquitin-proteasome pathway as cells exit mitosis.
    Localisation During interphase, PLK1 localizes to centrosomes. In early mitosis, it associates with mitotic spindle poles. A recombinant GFP-PLK1 protein localizes to centromere/kinetochore region, suggesting a possible role for chromosome separation.
    Function PLK1 is believed to be involved in the regulation of key steps during cell division, DNA damage repair pathways, apoptosis, and the progression of the cell cycle.
    PLK1 has roles in the activation of cdc2 through cdc25 and direct phosphorylation of cyclin B1, through which MPF (mitosis promoting factor) is activated so that mitosis can start.
    Microinjection of PLK1 antibodies causes failure of g-tubulin recruitment to the centrosomes. This failure results in immature centrosomes and monopolar spindle formation. Similar microinjection experiments in cell lines (transformed HeLa and non-immortalized Hs68 fibroblasts) result in a marked inhibition of cell cycle progression.
    PLK1 also has a possible role during cytokinesis based on the observation that PLK1 interacts and co-localizes with a kinesin related motor protein (CHO1/MKLP-1) at the interzone during anaphase and the mid-body during telophase and cytokinesis.
    Evidence suggests that BRCA2 is a substrate of PLK1 both in response to DNA damage and during normal cell cycle progression. This suggests a role for PLK1 in regulating DNA damage repair.
    Other studies have shown that the loss of PLK1 expression can induce pro-apoptotic pathways and inhibit growth.
    Based on yeast and murine studies of meiosis, human PLK1 may also have a regulatory function in meiosis. S. cerevisiae polo kinase CDC5 is required to phosphorylate and remove meiotic cohesion during the first cell division. In CDC5 depleted cells, kinetochores are bioriented during meiosis I, and Mam1, a protein essential for coorientation, fails to associate with kinetochores. CDC5 is believed to have roles in sister-kinetochore coorientation and chromosome segregation during meiosis I..
    Homology P.troglodytes: PLK1, polo-like kinase, XP_510879.1, 735 aa
    M.musculus: Plk1, polo-like kinase 1 (Drosophila), NP_035251.2, 603 aa
    R.norvegicus: Plk1, polo-like kinase 1 (Drosophila), NP_058796.1, 603 aa
    D.melanogaster: polo, polo, NP_524179.2, 576 aa
    C.elegans: plk-1 PoLo Kinase, NP_741243.1, 649 aa
    S.cerevisiae: CDC5, NP_013714.1, 705 aa

    Implicated in

    Note Increased PLK1 levels are detected in a variety of cancers.
    Disease Increased PLK1 transcript has been detected in a variety of tumor types including esophageal, head and neck squamous cell, liver, lung and breast carcinomas. Immunohistochemical studies also demonstrate increased PLK1 protein levels in melanomas, breast, ovarian, prostate cancers, and head, neck squamous cell carcinomas.
    Prognosis Statistically significant correlations between increased PLK1 expression and decreased patient survival suggest that PLK1 is a negative prognostic indicator for some types of cancer. For example,
  • In prostate cancer, PLK1 overexpression is linked to higher tumor grades
  • In non-Hodgkin's lymphomas, PLK1 overexpression reflect malignancy potentials
  • In hepatoblastomas, ovarian, colorectal cancers and melanomas, PLK1 overexpression suggests PLK1 to be a poor-prognostic indicator.
    • Oncogenesis Oncogenic properties of PLK1 are believed to be due to its role in driving cell cycle progression. Supporting evidence comes from the overexpression studies of PLK1 in NIH3T3 cell line. These cells become capable of forming foci and growing in soft agar and more importantly, these cells can form tumors in nude mice due to PLK1 overexpression.

    PLK1 has also been linked to known pathways that are altered during the neoplastic transformation. Retinoblastoma tumor suppressor (RB) pathway activation results in the repression of PLK1 promoter in a SWI/SNF chromatin remodeling complex dependent manner. In case of RB inactivation, PLK1 expression seems to be deregulated. This new finding suggests that PLK1 may be a target of the retinoblastoma tumor suppressor (RB) pathway.

    Moreover, PLK1 seems to be involved in the tumor suppressor p53 related pathways. Evidence suggests that PLK1 can inhibit transactivation and pro-apoptotic functions of p53 function by physical interaction and phosphorylation.

    In addition to PLK1šs role in normal cell cycle regulation, its connection to such known tumor suppressors may be crucial for the tumorigenesis processes.

      

    To be noted

    A study also suggests that PLK1 protein cannot be detected in normal brain tissue but it can be detected in brain tissues from Alzheimeršs disease patients.

    External links

    Nomenclature
    HGNC (Hugo)PLK1   9077
    Entrez_Gene (NCBI)PLK1  5347  polo-like kinase 1 (Drosophila)
    Cards
    AtlasPLK1ID41747ch16p12
    GeneCards (Weizmann)PLK1
    Ensembl (Hinxton)ENSG00000166851 [Gene_View]  PLK1 [Vega]
    AceView (NCBI)PLK1
    Genatlas (Paris)PLK1
    euGene (Indiana)5347
    SOURCE (Stanford)NM_005030
    Gene Expression (Array Express) ENSG00000166851
    Genomic and cartography
    GoldenPath (UCSC)PLK1  -  16p12.1   chr16:23597702-23609189 +  16p12.2   [Description]    (hg18-Mar_2006)
    EnsemblPLK1 - 16p12.2 [CytoView]
    Mapping of homologs : NCBIPLK1 [Mapview]
    OMIM602098   
    Gene and transcription
    Gene : Genbank (Entrez)AB084459 AB209179 AK303263 AK308276 AK313227
    Reference sequence (RefSeq transcript) :SRSNM_005030
    Reference transcript : EntrezNM_005030
    RefSeq genomic : SRSAC_000059 AC_000148 NC_000016 NT_010393 NW_001838401 NW_926217
    RefSeq genomic : EntrezAC_000059 AC_000148 NC_000016 NT_010393 NW_001838401 NW_926217
    Consensus coding sequences : CCDS NCBIPLK1
    Cluster EST : UnigeneHs.592049 [ SRS ] Hs.592049 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)5480
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtP53350 (SRS) P53350 (Expasy) P53350 (Uniprot)
    With graphics : InterProP53350
    Splice isoforms : VarSplice FASTAP53350(VarSplice FASTA)
    Domaine pattern : Prosite (SRS)POLO_BOX (PS50078)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
    Domain pattern : Prosite (Expaxy)POLO_BOX (PS50078)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
    Domains : Interpro (SRS)Ca/CaM-dep_prot_kinase-like    Kinase-like_dom    POLO_box_duplicated_dom    POLO_box_duplicated_dom_subgr    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    Se/Thr_prot_kinase-like_dom    Ser/Thr_prot_kinase_AS    Ser/Thr_prot_kinase_dom    Ser/Thr_prot_kinase_Polo-like   
    Domains : Interpro (EBI)Ca/CaM-dep_prot_kinase-like    Kinase-like_dom    POLO_box_duplicated_dom    POLO_box_duplicated_dom_subgr    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    Se/Thr_prot_kinase-like_dom    Ser/Thr_prot_kinase_AS    Ser/Thr_prot_kinase_dom    Ser/Thr_prot_kinase_Polo-like   
    Related proteins : CluSTrP53350
    Domain families : Pfam SRSPkinase (PF00069)    POLO_box (PF00659)   
    Domain families : Pfam SangerPkinase (PF00069)    POLO_box (PF00659)   
    Domain families : Pfam NCBIpfam00069    pfam00659   
    Domain families : Smart EMBLS_TKc (SM00220)  
    Blocks (Seattle)P53350
    Crystal structure of protein : PDB SRS1Q4K    1Q4O    1UMW    2OGQ    2OJX    2OU7    2OWB    2RKU    2V5Q    3BZI    3C5L    3FC2    3FVH    3HIH    3HIK   
    Crystal structure of protein : PDBSum1Q4K    1Q4O    1UMW    2OGQ    2OJX    2OU7    2OWB    2RKU    2V5Q    3BZI    3C5L    3FC2    3FVH    3HIH    3HIK   
    Crystal structure of protein : IMB1Q4K    1Q4O    1UMW    2OGQ    2OJX    2OU7    2OWB    2RKU    2V5Q    3BZI    3C5L    3FC2    3FVH    3HIH    3HIK   
    Crystal structure of protein : PDB RSDB1Q4K    1Q4O    1UMW    2OGQ    2OJX    2OU7    2OWB    2RKU    2V5Q    3BZI    3C5L    3FC2    3FVH    3HIH    3HIK   
    HPRD03652
    Protein Interaction databases
    DIP (DOE-UCLA)P53350
    IntAct (EBI)P53350
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIPLK1
    SNP : GeneSNP UtahPLK1
    SNP : HGBasePLK1
    Genetic variants : HAPMAPPLK1
    Somatic Mutations in Cancer : COSMICPLK1 
    Mutations and Diseases : HGMDPLK1
    Hereditary diseases : OMIM602098   
    Hereditary diseases : GENETests602098   
    Diseases : Genetic AssociationPLK1
    General knowledge
    Homologs : HomoloGenePLK1
    Homology/Alignments : Family Browser UCSCPLK1
    Phylogenetic Trees/Animal Genes : TreeFamPLK1
    Catalytic activity : Enzyme2.7.11.21 [ Enzyme-Expasy ]   2.7.11.21 [ Enzyme-SRS ]   2.7.11.21 [ IntEnz-EBI ]   2.7.11.21 [ BRENDA ]   2.7.11.21 [ KEGG ]   
    Chemical/Protein Interactions : CTD5347
    Keywords Ontology : AmiGOnucleotide binding  mitotic prometaphase  kinetochore  spindle pole  protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  cytoplasm  centrosome  cytosol  protein amino acid phosphorylation  cell cycle  cell proliferation  transferase activity  polar body extrusion after meiotic divisions  polo kinase kinase activity  response to antibiotic  spindle midzone  cell division  positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle  
    Keywords Ontology : EGO-EBInucleotide binding  mitotic prometaphase  kinetochore  spindle pole  protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  cytoplasm  centrosome  cytosol  protein amino acid phosphorylation  cell cycle  cell proliferation  transferase activity  polar body extrusion after meiotic divisions  polo kinase kinase activity  response to antibiotic  spindle midzone  cell division  positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle  
    Pathways : BIOCARTACell Cycle: G2/M Checkpoint [Genes]   
    Pathways : KEGGCell cycle
    Other databases
    Probes
    Probes : ImagenesPLK1 Related clones (RZPD - Berlin)
    Literature
    PubMed207 Pubmed reference(s) in Entrez
    PubGenePLK1

    Bibliography

    Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase.
    Lake RJ, Jelinek WR
    Molecular and cellular biology. 1993 ; 13 (12) : 7793-7801.
    PMID 7902533
     
    Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5.
    Golsteyn RM, Schultz SJ, Bartek J, Ziemiecki A, Ried T, Nigg EA
    Journal of cell science. 1994 ; 107 ( Pt 6) : 1509-1517.
    PMID 7962193
     
    Cloning and characterization of human and murine homologues of the Drosophila polo serine-threonine kinase.
    Hamanaka R, Maloid S, Smith MR, O'Connell CD, Longo DL, Ferris DK
    Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1994 ; 5 (3) : 249-257.
    PMID 8018557
     
    Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1.
    Lee KS, Yuan YL, Kuriyama R, Erikson RL
    Molecular and cellular biology. 1995 ; 15 (12) : 7143-7151.
    PMID 8524282
     
    Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.
    Lane HA, Nigg EA
    The Journal of cell biology. 1996 ; 135 (6 Pt 2) : 1701-1713.
    PMID 8991084
     
    The mouse Plk gene: structural characterization, chromosomal localization and identification of a processed Plk pseudogene.
    Clay FJ, Ernst MR, Trueman JW, Flegg R, Dunn AR
    Gene. 1997 ; 198 (1-2) : 329-339.
    PMID 9370299
     
    Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase.
    Smith MR, Wilson ML, Hamanaka R, Chase D, Kung H, Longo DL, Ferris DK
    Biochemical and biophysical research communications. 1997 ; 234 (2) : 397-405.
    PMID 9177283
     
    GFP tagging reveals human Polo-like kinase 1 at the kinetochore/centromere region of mitotic chromosomes.
    Arnaud L, Pines J, Nigg EA
    Chromosoma. 1998 ; 107 (6-7) : 424-429.
    PMID 9914374
     
    Polo-like kinases: a team that plays throughout mitosis.
    Glover DM, Hagan IM, Tavares AA
    Genes & development. 1998 ; 12 (24) : 3777-3787.
    PMID 9869630
     
    Neuronal polo-like kinase in Alzheimer disease indicates cell cycle changes.
    Harris PL, Zhu X, Pamies C, Rottkamp CA, Ghanbari HA, McShea A, Feng Y, Ferris DK, Smith MA
    Neurobiology of aging. 2000 ; 21 (6) : 837-841.
    PMID 11124427
     
    Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer.
    Wolf G, Hildenbrand R, Schwar C, Grobholz R, Kaufmann M, Stutte HJ, Strebhardt K, Bleyl U
    Pathology, research and practice. 2000 ; 196 (11) : 753-759.
    PMID 11186170
     
    Expression of polo-like kinase (PLK1) in thin melanomas: a novel marker of metastatic disease.
    Kneisel L, Strebhardt K, Bernd A, Wolter M, Binder A, Kaufmann R
    Journal of cutaneous pathology. 2002 ; 29 (6) : 354-358.
    PMID 12135466
     
    Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation.
    Lee BH, Amon A
    Science (New York, N.Y.). 2003 ; 300 (5618) : 482-486.
    PMID 12663816
     
    M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex.
    Lin HR, Ting NS, Qin J, Lee WH
    The Journal of biological chemistry. 2003 ; 278 (38) : 35979-35987.
    PMID 12815053
     
    Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells.
    Liu X, Erikson RL
    Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (10) : 5789-5794.
    PMID 12732729
     
    Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers.
    Takahashi T, Sano B, Nagata T, Kato H, Sugiyama Y, Kunieda K, Kimura M, Okano Y, Saji S
    Cancer science. 2003 ; 94 (2) : 148-152.
    PMID 12708489
     
    Polo-like kinase 1 and Chk2 interact and co-localize to centrosomes and the midbody.
    Tsvetkov L, Xu X, Li J, Stern DF
    The Journal of biological chemistry. 2003 ; 278 (10) : 8468-8475.
    PMID 12493754
     
    Polo-like kinase 1 (Plk1) inhibits p53 function by physical interaction and phosphorylation.
    Ando K, Ozaki T, Yamamoto H, Furuya K, Hosoda M, Hayashi S, Fukuzawa M, Nakagawara A
    The Journal of biological chemistry. 2004 ; 279 (24) : 25549-25561.
    PMID 15024021
     
    Hierarchical requirement of SWI/SNF in retinoblastoma tumor suppressor-mediated repression of Plk1.
    Gunawardena RW, Siddiqui H, Solomon DA, Mayhew CN, Held J, Angus SP, Knudsen ES
    The Journal of biological chemistry. 2004 ; 279 (28) : 29278-29285.
    PMID 15105433
     
    Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1.
    Hansen DV, Loktev AV, Ban KH, Jackson PK
    Molecular biology of the cell. 2004 ; 15 (12) : 5623-5634.
    PMID 15469984
     
    Phosphorylation of BRCA2 by the Polo-like kinase Plk1 is regulated by DNA damage and mitotic progression.
    Lee M, Daniels MJ, Venkitaraman AR
    Oncogene. 2004 ; 23 (4) : 865-872.
    PMID 14647413
     
    Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells.
    Lindon C, Pines J
    The Journal of cell biology. 2004 ; 164 (2) : 233-241.
    PMID 14734534
     
    Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1.
    Liu X, Zhou T, Kuriyama R, Erikson RL
    Journal of cell science. 2004 ; 117 (Pt 15) : 3233-3246.
    PMID 15199097
     
    Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma.
    Weichert W, Denkert C, Schmidt M, Gekeler V, Wolf G, Kˆbel M, Dietel M, Hauptmann S
    British journal of cancer. 2004 ; 90 (4) : 815-821.
    PMID 14970859
     
    Polo-like kinase 1 is overexpressed in prostate cancer and linked to higher tumor grades.
    Weichert W, Schmidt M, Gekeler V, Denkert C, Stephan C, Jung K, Loening S, Dietel M, Kristiansen G
    The Prostate. 2004 ; 60 (3) : 240-245.
    PMID 15176053
     
    Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.
    Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A
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    PMID 15221005
     
    Polo-like kinases and oncogenesis.
    Eckerdt F, Yuan J, Strebhardt K
    Oncogene. 2005 ; 24 (2) : 267-276.
    PMID 15640842
     
    Expression of Polo-Like Kinase (PLK1) in non-Hodgkin's lymphomas.
    Mito K, Kashima K, Kikuchi H, Daa T, Nakayama I, Yokoyama S
    Leukemia & lymphoma. 2005 ; 46 (2) : 225-231.
    PMID 15621805
     
    Polo-like kinases (Plks) and cancer.
    Takai N, Hamanaka R, Yoshimatsu J, Miyakawa I
    Oncogene. 2005 ; 24 (2) : 287-291.
    PMID 15640844
     
    Differential regulation of polo-like kinase 1, 2, 3, and 4 gene expression in mammalian cells and tissues.
    Winkles JA, Alberts GF
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    PMID 15640841
     
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    Contributor(s)

    Written04-2005Ayse Elif Erson, Elizabeth M. Petty

    Citation

    This paper should be referenced as such :
    Erson AE, Petty EM . PLK1 (polo-like kinase 1 (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. April 2005 .
    URL : http://AtlasGeneticsOncology.org/Genes/PLK1ID41747ch16p12.html

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